Podocyte-Specific Protein Expression in Urine Exosome Acts as a Marker for Renal Injury in Post-COVID State

<b><i>Introduction:</i></b> Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) has been associated with the development of COVID-19. COVID-19 may cause endothelial cell dysfunction (ECD), which can lead to cardiometabolic diseases and podocytopathy. In this study, we explored whether presence of hyperglycemia predisposes to SARS-CoV-2 infection, <i>in vitro</i>, and whether COVID-19 can put an individual at a higher risk of persistent renal damage in the long-term following acute COVID infection. To estimate renal damage, we evaluated albuminuria and podocytopathy. Podocytopathy was estimated by measuring podocyte-specific protein levels in urine-derived exosomes from patients who were admitted with acute COVID-19 at 10 days, 6 months, and 12 months post-acute SARS-CoV-2 infection. <b><i>Methods:</i></b> Blood and urine samples from patients with SARS-CoV-2 post-infection were procured from the George Washington University COVID repository. Peripheral blood mononuclear cells and urine exosomes were isolated. Podocyte-specific proteins Podocalyxin (PODXL) and Nephrin (NEPH) were identified from urine exosomes. <b><i>Results:</i></b> Urine exosomal podocalyxin levels were significantly high at 10 week (<i>n</i> = 18; <i>P</i> = 0.001), 6 month (<i>n</i> = 25; <i>P</i> = 0.003) and 12 month (<i>n</i> = 14; <i>P</i> = 0.0001) time points. Nephrin levels were also noted to be high at 10 week (<i>n</i> = 18; <i>P</i> = 0.001) and 12 month (<i>n</i> = 14; <i>P</i> = 0.007) time points, compared with urine samples obtained from type 2 diabetes subjects who never had COVID-19. Though urinary podocyte-specific proteins were high, compared to control, there were no significant differences noted on urine albumin:creatinine ratios (UACR) between the groups. <b><i>Conclusion:</i></b> Persistent high levels of podocyte-specific proteins noted in urinary exosomes even at 12 months post-Covid may lead to the development of chronic kidney disease.